We define cancer equity as all people having as the same opportunity for cancer prevention, treatment, and survivorship care. However, marginalized populations continue to experience avoidable and unjust disparities in cancer care, access to clinical trials, and cancer survival. Racial and ethnic minorities, and individuals with low socioeconomic status, Medicaid insurance, limited health literacy, disabilities, and mental health disorders are more likely to experience delays to cancer diagnosis and less likely to receive guideline-concordant cancer care. These disparities are impacted by the social determinants of health including structural discrimination, racism, poverty, and inequities in access to healthcare and clinical trials. There is an urgent need to develop and adapt evidence-based interventions in collaboration with community partners that have potential to address the social determinants of health and build capacity for cancer care for underserved populations. We established the Virtual Equity Hub by developing a collaborative network connecting a comprehensive cancer center, academic safety net hospital, and community health centers and affiliates. The Virtual Equity Hub utilizes a virtual tumor board, an evidence-based approach that increases access to multi-specialty cancer care and oncology subspecialty expertise. We adapted the tumor board model by engaging person-centered teams of multi-disciplinary specialists across health systems, addressing the social determinants of health, and applying community-based research principles with a focus on populations with poor cancer survival. The virtual tumor board included monthly videoconferences, case discussion, sharing of expertise, and a focus on addressing barriers to care and trial participation. Specifically, we piloted virtual tumor boards for breast oncology, neuro-oncology, and individuals with cancer and serious mental illness. The Virtual Equity Hub demonstrated promise at building capacity for clinicians to care for patients with complex needs and addressing barriers to care. Research is needed to measure the impact, reach, and sustainability of virtual equity models for patients with cancer.Despite rapid advances in cancer treatment, disparities in cancer care persist. This article describes a virtual tumor board developed to provide a collaborative network of multi-disciplinary specialists, which showed promise at building capacity for clinicians to care for patients with complex needs and addressing barriers to care. 相似文献
Rotaviruses (RVs) preferentially replicate in the small intestine and frequently cause severe diarrheal disease, and the following enteric infection generally induces variable levels of protective systemic and mucosal immune responses in humans and other animals. Rhesus rotavirus (RRV) is a simian RV that was previously used as a human RV vaccine and has been extensively studied in mice. Although RRV replicates poorly in the suckling mouse intestine, infection induces a robust and protective antibody response. The recent availability of plasmid only-based RV reverse genetics systems has enabled the generation of recombinant RVs expressing foreign proteins. However, recombinant RVs have not yet been experimentally tested as potential vaccine vectors to immunize against other gastrointestinal pathogens in vivo. This is a newly available opportunity because several live-attenuated RV vaccines are already widely administered to infants and young children worldwide. To explore the feasibility of using RV as a dual vaccine vector, we rescued replication-competent recombinant RRVs harboring bicistronic gene segment 7 that encodes the native RV nonstructural protein 3 (NSP3) protein and a human norovirus (HuNoV) VP1 protein or P domain from the predominant genotype GII.4. The rescued viruses expressed HuNoV VP1 or P protein in infected cells in vitro and elicited systemic and local antibody responses to HuNoV and RRV following oral infection of suckling mice. Serum IgG and fecal IgA from infected suckling mice bound to and neutralized both RRV and HuNoV. These findings have encouraging practical implications for the design of RV-based next-generation multivalent enteric vaccines to target HuNoV and other human enteric pathogens.Mucosal immunity plays a critical role in protecting against many pathogens in the respiratory and intestinal tracts. Live virus infections generally trigger more robust and effective mucosal immune response than oral administration of inactivated viruses or target protein antigens because they are self-amplifying and can more effectively elicit cellular as well as humoral immunity (1–4). Several studies have attempted to utilize recombinant viruses as vaccine vectors to induce an immune response against enteric pathogens (5–8); however, the most advanced of such enteric vaccine vectors are still in early stages of clinical development.Rotaviruses (RVs), the leading cause of acute gastroenteritis in infants, are a promising candidate for enteric vaccine vectors for several reasons. A) RV preferentially replicates in the small intestine, distinguishing it from several other enteric viruses that can also infect systemically or the colon. B) RV infection is acute, and the virus does not integrate into the host genome. C) RV is highly immunogenic and induces both systemic and mucosal immune responses in infected animals and humans (9, 10). D) Several live-attenuated human RV vaccines have been shown to be both safe and effective to use in very young children [e.g., RotaTeq (Merck) and Rotarix (GlaxoSmithKline)]. Other effective live-attenuated RV vaccines [Rotasiil, Rotavac, Lanzhou lamb rotavirus vaccine (LLR), and Rotavin-M1] are also licensed for use globally or primarily in their country of origin (11). E) Following substantial public health efforts, RV vaccines are now widely available in many low- and middle-income countries, as well as the more developed countries, and hence the administration of RV-based vaccines that included other heterologous antigens could potentially be piggybacked onto current RV immunization programs used globally. F) The RV double-stranded RNA (dsRNA) genome is segmented in nature, permitting easy genetic manipulation. G) With the insertion of heterologous antigens, RV replication can become attenuated in vitro (12, 13).Since a plasmid-based reverse genetics system was established in 2017, several studies have reported the generation of recombinant RVs that express fluorescent and bioluminescent reporter proteins (GFP, RFP, luciferase, etc.) and exogenous nucleotide sequences [e.g., endoribonuclease Csy4 target sequence and sequences encoding the receptor binding domain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein] in vitro (12–22). To facilitate the assessment and development of RVs as potential enteric vaccine vectors, the capacity of recombinant RVs to induce an enteric immune response against other gastrointestinal (GI) pathogens needs to be evaluated in well-characterized preclinical small animal models. Rhesus rotavirus (RRV) is a prototype laboratory strain of simian RV that efficiently replicates in vitro (23, 24). Although RRV does not replicate well in a murine model (25–27), it does induce both systemic and mucosal immune responses in infected mice (28). In addition, RRV itself and RRV-based RV vaccine candidates have previously been shown to be a highly immunogenic and protective in several human vaccine trials and were, for a time, licensed for use in children in the United States (29, 30).Human norovirus (HuNoV) is a major cause of acute gastroenteritis in both young children and adults. Although B cells and human intestinal organoids support HuNoV replication (31, 32), there is not yet a widely available robust cell culture system for efficient HuNoV cultivation, which has impeded both the assessment of HuNoV immunity and vaccine development. The HuNoV virion consists of major capsid protein VP1 and minor capsid protein VP2 surrounding a positive-sense RNA genome (33–35). Exogenously expressed VP1 can form virus-like particles (VLPs) that are structurally and antigenically similar to HuNoV virions (36–38), and the parenteral administration of such VLPs provides some level of protective immunity to HuNoV in adults (39–41). Moreover, expression of the protruding or P domain of VP1 that bears the major antigenic sites of HuNoV can yield subunit “P particles” that can also induce immune responses (42, 43). Here, we demonstrate the induction of both systemic and mucosal antibody responses against HuNoV in suckling mice using recombinant RRVs expressing HuNoV VP1 or P domain. Our data suggest that recombinant RVs represent a potentially effective small-intestine–targeted vaccination platform to express exogenous genes in the human intestine and to protect people from other enteric pathogens such as HuNoV as well as RV. 相似文献
It is appropriate that our theme this afternoon is ‘driving change’. It is evident that our society is addicted to, some would say afflicted by, change and that older people, like everyone else are caught up in the process. It may be also that many of us who grew up in more stable, less dynamic times find it more difficult to deal with. My argument, however, is that we should not. That at least is the import of the quotation from Eliot's Four Quartets which gives me my title: Old men ought to be explorers Here and there does not matter We must be still and still moving Into another intensity. (Eliot, 1948: 22). 相似文献
The aim of this study was to explore the association between different types of headache (HA) and the clinical features of multiple sclerosis (MS). The relationship between HA and MS-specific therapies was also analysed. A total of 102 MS patients were recruited at the MS Centre of S. Andrea Hospital in Rome. According to International Headache Society criteria, the lifetime prevalence of primary HA was 61.8%. Migraine was observed more often in young relapsing-remitting MS patients, whilst tension-type HA was associated with older age, male gender and a secondary progressive course. Sixty-four patients had a history of ongoing or past interferon beta (IFNb) exposure. Of these, 17 subjects did not have a history of HA, while 24 complained of an increase in frequency of migraine attacks and 7 reported an IFNb-induced HA. Investigating and treating HA in MS patients starting IFNb therapy may improve MS-specific medication compliance.
Innate immune responses are critical in the defense against viral infections. NK cells, myeloid and plasmacytoid dendritic cells, and invariant CD1d-restricted NKT cells mediate both effector and regulatory functions in this early immune response. In chronic uncontrolled viral infections such as HCV and HIV-1, these essential immune functions are compromised and can become a double edged sword contributing to the immunopathogenesis of viral disease. In particular, recent findings indicate that innate immune responses play a central role in the chronic immune activation which is a primary driver of HIV-1 disease progression. HCV/HIV-1 co-infection is affecting millions of people and is associated with faster viral disease progression. Here, we review the role of innate immunity and chronic immune activation in HCV and HIV-1 infection, and discuss how mechanisms of innate immunity may influence protection as well as immunopathogenesis in the HCV/HIV-1 co-infected human host. 相似文献